HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Related articles in The JI Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carroll, T. D. Articles by Miller, C. J. Search for Related Content PubMed PubMed Citation Articles by Carroll, T. D. Articles by Miller, C. J.

Interferon-Induced Expression of MxA in the Respiratory Tract of Rhesus Macaques Is Suppressed by Influenza Virus Replication¹

Timothy D. Carroll^*,, Shannon R. Matzinger^*,, Meritxell Genescà^*,, Linda Fritts^*,, Roxana Colòn^*, Michael B. McChesney^*, and Christopher J. Miller^2,*,,

^* California National Primate Research Center, Center for Comparative Medicine, Department of Pathology and Laboratory Medicine, School of Medicine, and Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616

To determine the relationship between influenza A virus replication and innate antiviral immune responses, rhesus monkeys were given oseltamivir before influenza A/Memphis/7/01 (H1N1) challenge. We found that oseltamivir treatment significantly reduced viral replication in the trachea (p < 0.029). Further, in the trachea of both treated and untreated monkeys the mRNA levels of most innate antiviral molecules in the IFN-β pathway were dramatically increased by 24 h postinfection. However, the mRNA level of a single IFN-stimulated gene, MxA (myxovirus resistance A), the IFN-stimulated gene known to be critical in blocking influenza virus replication, was significantly lower in the tracheal lavages of untreated monkeys than in the oseltamivir-treated monkeys (p = 0.05). These results demonstrate for the first time that uncontrolled influenza A virus replication actively suppresses MxA gene expression and emphasize the critical role of innate immunity in controlling influenza virus replication in vivo.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants P51 RR11069, U01 AI57264, and U01 AI5726.

² Address correspondence and reprint requests to Dr. Christopher J. Miller, California National Primate Research Center, University of California, One Shields Avenue, Davis, CA 95616. E-mail address: cjmiller{at}ucdavis.edu

³ Abbreviations used in this paper: ISG, IFN-stimulated gene; CPE, cytopathic effect; HI, hemagglutinin inhibition; IP-10, IFN-inducible protein 10; ISRE, IFN-β-stimulated response element; MDCK, Madin-Darby canine kidney; Mx, myxovirus-resistance protein; OAS, 2'-5'-oligoadenylate synthetase; PI, postinfection; TCID₅₀, 50% tissue culture infectious dose; vRNA, viral RNA.

Related articles in The JI:

IN THIS ISSUE

The JI 2008 180: 2005-2006. [Full Text]  

This article has been cited by other articles:

				A. Sexton, R. De Rose, J. C. Reece, S. Alcantara, L. Loh, J. M. Moffat, K. Laurie, A. Hurt, P. C. Doherty, S. J. Turner, et al. Evaluation of Recombinant Influenza Virus-Simian Immunodeficiency Virus Vaccines in Macaques J. Virol., August 1, 2009; 83(15): 7619 - 7628. [Abstract] [Full Text] [PDF]